Photosensitive EpilepsyPhase 2/3NCT03580707
Does BRV Have Faster Onset Time & Greater Effect Than LEV in Epilepsy Pts Using PPR Pharmacodynamic Efficacy Endpoint
A Phase 2/3 study testing BRV vs LEV in randomized double blinded, crossover fashion in people with Photosensitive Epilepsy, run by Rosenfeld, William E., M.D. at 1 site in United States.
Trial summary
The main purpose of this study is to see whether brivaracetam has a faster onset time and greater effect than levetiracetam in subjects with photosensitive seizures. Part 1 of the study will compare the effects of levetiracetam 1500 mg with the effects of brivaracetam 100 mg. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Photosensitive Epilepsy
- What is being tested?
- BRV vs LEV in randomized double blinded, crossover fashion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2018to 31 Dec 2018
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients between 18 and 65 years of age
- Male or female
- PPR at minimum at 60,50,40,30,25,20,18 or 16 Hz as upper threshold
- Drug naïve or at most with up to 4 AEDs, not being LEV or BRV
Who cannot join
- Current treatment with more than 4 AEDs
- LEV or BRV as current treatment or used in the previous month.
- History of severe side-effects or psychological side-effects with LEV or BRV use
- Being pregnant or insufficiently protected against pregnancy (see also ref 31) or lactating Female
- Serious internal medical disease (renal/hepatic/cardiovascular disease) as deemed by the on-site physician (WER)
- History of psychiatric disease that has been a reason for acute hospitalisation for their condition of depression, schizophrenia, mania, delirium or aggressive behaviour
- History of status epilepticus
- History of significant ethanol or illicit drug use
Trial locations and contacts
1 site in 1 country.
United States1 site
The Comprehensive Epilepsy Care Center For Children And Adults
St Louis, Missouri, 63141
About this study
Official title: Does BRV Have a Faster Onset Time and Greater Effect Than LEV in Epilepsy Patients?: A Prospective, Randomized, Crossover, Double-blind, Controlled Intravenous Study Using the PPR as a Pharmacodynamic Efficacy Endpoint
The main purpose of this study is to see whether brivaracetam has a faster onset time and greater effect than levetiracetam in subjects with photosensitive seizures. Part 1 of the study will compare the effects of levetiracetam 1500 mg with the effects of brivaracetam 100 mg. Part 2, will compare the effects of levetiracetam 1500 mg with the effects of brivaracetam 100 mg or will compare the effects of levetiracetam 500mg with the effects of brivaracetam 25 mg.
Read the detailed description
The proposed study in epilepsy patients with photosensitivity intends to extend the animal findings for the faster (and perhaps greater) pharmacodynamic effect of intravenous BRV versus LEV at equipotent doses. Doses and infusion times were chosen based on proven safety profiles of both drugs (UCB, data on file): maximal dose of 1500 mg LEV in 15 minutes (or in 5 minutes) and 100 mg for BRV (15 times more potency of BRV compared to LEV). The study proposes a comparison of the rapidity of the CNS effects of both LEV and BRV within the same patient (randomized, two-way crossover, double-blind in a total 16 patients with epilepsy 8 patients in Part 1 and 8 patients in Part 2) Study Part 1: an IV infusion over 15 minutes, appropriately diluted (per package insert for LEV); BRV will also be administered as a 15-minute infusion (anticipating similar language in the package insert for BRV);Study Part 2, Option I: Assuming a statistically significant difference in the rapidity of CNS action has been observed from an analysis of the data set in Study Part 1, will proceed with Study Part 2 Option I. LEV or BRV will be administered, in a randomized, two-way crossover, double-blind design as an IV infusion over 5 minutes, appropriately diluted, to another cohort of 8 patients with photosensitive epilepsy. (Potentially, a few of the same patients as under 'a' above could participate herein, if they are willing to repeat the study). OR Study Part 2, Option II: Assuming no statistically significant difference in the rapidity of CNS action has been observed from an analysis of the data set in Study Part 1, will proceed with Study Part 2, Option II. LEV or BRV will be administered, in a randomized, two-way crossover, double-blind design as an IV infusion over again 15 minutes, appropriately diluted, to another cohort of 8 patients with photosensitive epilepsy. (Potentially, a few of the same patients as under 'a' above could participate herein, if they are willing to repeat the study). However, LEV will be given as a 500 mg dose, and BRV as a 25 mg dose. Use of lower, nearly equipotent minimally effective doses of LEV and BRV will maximize ability to readily differentiate the electroencephalographic PPR effect between the two AEDs.
- Conditions
- Photosensitive Epilepsy
- Being tested
- BRV vs LEV in randomized double blinded, crossover fashion
- Medical subject headings
- Epilepsy, Reflex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BRV vs LEV in randomized double blinded, crossover fashionDrug
Also called Intermit pho stim respect over 2 hours/each of 2 study days
Single dose intravenous administration of BRV 100 mg over a 15 minutes period. On a subsequent occasion, (approximately 2 weeks later), the patient is crossed over to the other drug at a singular dose. On both occasions, intermittent photic stimulation is done 10 times in a two hour period. IPS is again conducted in the cross over portion as well. Coincident with IPS stimulation 10 blood samples will be drawn for BRV or LEV plasma concentration.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Active comparator | Compare rapidity of CNS effects of levetiracetam (LEV) \& brivaracetam (BRV) within same pt-(randomized, two-way crossover, dbl-blind in total 16 pts w/epilepsy. Pt 1: IV infusion over 15 min BRV will also be administered as 15-min.infusion. BRV vs LEV in randomized double blinded, crossover fashion. Receives: Drug: BRV vs LEV in randomized double blinded, crossover fashion |
| Part 2 | Active comparator | Pt 2 Op I:Assuming statistically signify. diff. in rapidity of CNS action has been observed from an analysis of data set in Pt 1,will proceed w/ Pt 2Opt I. Levetiracetam (LEV) or brivaracetam (BRV administered in randomized, two-way crossover, dbl-blind design as IV infusion over 5 min. to another cohort of 8 pts w/photosensitive epilepsy OR Pt 2,Opt II: Assuming no statistically signif. diff. in rapidity of CNS action has been observed from an analysis of data set in Pt 1, will proceed w/Pt 2,Opt II. LEV or BRV will be administered, in randomized, two-way crossover, dbl-blind design as IV infusion over again 15 min. to another cohort of 8 pts w/ photosensitive epilepsy. LEV will be given as 500 mg dose \& BRV as 25 mg dose. BRV vs LEV in randomized double blinded, crossover fashion. Receives: Drug: BRV vs LEV in randomized double blinded, crossover fashion |
What is being measured
The primary outcome is the main question the study is designed to answer.
"Comparison between Brivaracetam and Levetiracetam of the Time to Peak Effect (Abolition) and Time to >50% Diminution in Photo-Paroxysmal Response in Patients with Photosensitive Epilepsy" (1)
Difference in time (minutes) required between drugs, BRV\& LEV to abolish a PPR (photo-paroxysmal response on the pts encephalogram, EEG) after intermittent photic stimulation (IPS) tested in the same pt of 2 separate occasions. In Pt 1, 8 pts w/photosensitive epilepsy will be studied in double-blind, crossover fashion with 15-minute linear intravenous (i.v.) infusion of either 1500 mg LEV or BRV 100 mg as single dose. After 2 weeks, each pt will be tested in identical fashion w/opposite drug (crossover). Pt 2, Option 1, 8 pts w/photosensitive epilepsy will be studied in double-blind, crossover fashion. Same single mg doses of LEV and BRV will be used, but i.v. infusion time will be 5 minutes;primary outcome measure will be same.Part 2, Option 2, 8 pts w/photosensitive epilepsy will be studied in double-blind, crossover fashion. Single mg i.v. dose of 500 mg LEV or 25 mg BRV will be used, w/infusion time over 15 minutes;primary outcome measure will be the same.
Measured: Six weeks
Secondary outcomes (1)
"Comparison between Brivaracetam and Levetiracetam of the Time to Peak Effect (Abolition) and Time to >50% Diminution in Photo-Paroxysmal Response in Patients with Photosensitive Epilepsy" (2)
Difference in time (minutes) required between drugs,BRV \& LEV to produce a >50% decrease in PPR (photo-paroxysmal response on pts encephalogram, EEG) after intermittent photic stimulation (IPS) tested in same pt of 2 separate occasions. Pt 1, 8 patients w/photosensitive epilepsy will be studied in double-blind, crossover fashion w/15-minute linear intravenous (i.v.) infusion of either 1500 mg LEV or BRV 100 mg as single dose. After 2 weeks, each pt will be tested in identical fashion w/opposite drug (crossover). In Pt 2, Option 1, 8 pts w/photosensitive epilepsy will be studied in double-blind, crossover fashion. Same single mg doses of LEV and BRV will be used, but i.v. infusion time will be 5 minutes; primary outcome measure will be the same. Pt 2, Option 2, 8 pts w/photosensitive epilepsy will be studied in double-blind, crossover fashion. Single mg i.v. dose of 500 mg LEV or 25 mg BRV will be used, with infusion time over 15 minutes; primary outcome measure will be same.
Measured: Six weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2018
- Study start1 Jun 2018
- Primary completion31 Dec 2018
- Study completion31 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Photosensitive EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rosenfeld, William E., M.D.
- Collaborators
- Comprehensive Epilepsy Care Center for Children & Adults, Utrecht University, PRA Health Sciences, UCB Biopharma S.P.R.L.
- Responsible party
- Sponsor
- Investigators
- William E Rosenfeld, M.D., Principal investigator, Comprehensive Epilepsy Care Center for Children & Adults
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03580707
- Sponsor's protocol ID
- SAIRB-18-0016
- Status last verified
- Mar 2019
- First submitted
- 24 May 2018
- Last updated
- 26 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Reed RC, Rosenfeld WE, Lippmann SM, Eijkemans RMJC, Kasteleijn-Nolst Trenite DGA. Rapidity of CNS Effect on Photoparoxysmal Response for Brivaracetam vs. Levetiracetam: A Randomized, Double-blind, Crossover Trial in Photosensitive Epilepsy Patients. CNS Drugs. 2020 Oct;34(10):1075-1086. doi: 10.1007/s40263-020-00761-1.
PubMed 32949370
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does BRV Have a Faster Onset Time and Greater Effect Than LEV in Epilepsy Patients?: A Prospective, Randomized, Crossover, Double-blind, Controlled Intravenous Study Using the PPR as a Pharmacodynamic Efficacy Endpoint
- ClinicalTrials.gov ID
- NCT03580707
- Acronym / sponsor ID
- SAIRB-18-0016
- Conditions
- Photosensitive Epilepsy
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Rosenfeld, William E., M.D.
- Collaborators
- Comprehensive Epilepsy Care Center for Children & Adults, Utrecht University, PRA Health Sciences, UCB Biopharma S.P.R.L.
- Study start
- 1 Jun 2018 (actual)
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 9 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to see whether brivaracetam has a faster onset time and greater effect than levetiracetam in subjects with photosensitive seizures. Part 1 of the study will compare the effects of levetiracetam 1500 mg with the effects of brivaracetam 100 mg. Part 2, will compare the effects of levetiracetam 1500 mg with the effects of brivaracetam 100 mg or will compare the effects of levetiracetam 500mg with the effects of brivaracetam 25 mg.
Detailed description
The proposed study in epilepsy patients with photosensitivity intends to extend the animal findings for the faster (and perhaps greater) pharmacodynamic effect of intravenous BRV versus LEV at equipotent doses. Doses and infusion times were chosen based on proven safety profiles of both drugs (UCB, data on file): maximal dose of 1500 mg LEV in 15 minutes (or in 5 minutes) and 100 mg for BRV (15 times more potency of BRV compared to LEV). The study proposes a comparison of the rapidity of the CNS effects of both LEV and BRV within the same patient (randomized, two-way crossover, double-blind in a total 16 patients with epilepsy 8 patients in Part 1 and 8 patients in Part 2) Study Part 1: an IV infusion over 15 minutes, appropriately diluted (per package insert for LEV); BRV will also be administered as a 15-minute infusion (anticipating similar language in the package insert for BRV);Study Part 2, Option I: Assuming a statistically significant difference in the rapidity of CNS action has been observed from an analysis of the data set in Study Part 1, will proceed with Study Part 2 Option I. LEV or BRV will be administered, in a randomized, two-way crossover, double-blind design as an IV infusion over 5 minutes, appropriately diluted, to another cohort of 8 patients with photosensitive epilepsy. (Potentially, a few of the same patients as under 'a' above could participate herein, if they are willing to repeat the study). OR Study Part 2, Option II: Assuming no statistically significant difference in the rapidity of CNS action has been observed from an analysis of the data set in Study Part 1, will proceed with Study Part 2, Option II. LEV or BRV will be administered, in a randomized, two-way crossover, double-blind design as an IV infusion over again 15 minutes, appropriately diluted, to another cohort of 8 patients with photosensitive epilepsy. (Potentially, a few of the same patients as under 'a' above could participate herein, if they are willing to repeat the study). However, LEV will be given as a 500 mg dose, and BRV as a 25 mg dose. Use of lower, nearly equipotent minimally effective doses of LEV and BRV will maximize ability to readily differentiate the electroencephalographic PPR effect between the two AEDs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Active comparator | Drug: BRV vs LEV in randomized double blinded, crossover fashionCompare rapidity of CNS effects of levetiracetam (LEV) \& brivaracetam (BRV) within same pt-(randomized, two-way crossover, dbl-blind in total 16 pts w/epilepsy. Pt 1: IV infusion over 15 min BRV will also be administered as 15-min.infusion. BRV vs LEV in randomized double blinded, crossover fashion. |
| Part 2 | Active comparator | Drug: BRV vs LEV in randomized double blinded, crossover fashionPt 2 Op I:Assuming statistically signify. diff. in rapidity of CNS action has been observed from an analysis of data set in Pt 1,will proceed w/ Pt 2Opt I. Levetiracetam (LEV) or brivaracetam (BRV administered in randomized, two-way crossover, dbl-blind design as IV infusion over 5 min. to another cohort of 8 pts w/photosensitive epilepsy OR Pt 2,Opt II: Assuming no statistically signif. diff. in rapidity of CNS action has been observed from an analysis of data set in Pt 1, will proceed w/Pt 2,Opt II. LEV or BRV will be administered, in randomized, two-way crossover, dbl-blind design as IV infusion over again 15 min. to another cohort of 8 pts w/ photosensitive epilepsy. LEV will be given as 500 mg dose \& BRV as 25 mg dose. BRV vs LEV in randomized double blinded, crossover fashion. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients between 18 and 65 years of age
- Male or female
- PPR at minimum at 60,50,40,30,25,20,18 or 16 Hz as upper threshold
- Drug naïve or at most with up to 4 AEDs, not being LEV or BRV
Key exclusion criteria (8 listed)
- Current treatment with more than 4 AEDs
- LEV or BRV as current treatment or used in the previous month.
- History of severe side-effects or psychological side-effects with LEV or BRV use
- Being pregnant or insufficiently protected against pregnancy (see also ref 31) or lactating Female
- Serious internal medical disease (renal/hepatic/cardiovascular disease) as deemed by the on-site physician (WER)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BRV vs LEV in randomized double blinded, crossover fashionAlso: Intermit pho stim respect over 2 hours/each of 2 study daysSingle dose intravenous administration of BRV 100 mg over a 15 minutes period. On a subsequent occasion, (approximately 2 weeks later), the patient is crossed over to the other drug at a singular dose. On both occasions, intermittent photic stimulation is done 10 times in a two hour period. IPS is again conducted in the cross over portion as well. Coincident with IPS stimulation 10 blood samples will be drawn for BRV or LEV plasma concentration. | Drug | Part 1, Part 2 |
Primary outcome
"Comparison between Brivaracetam and Levetiracetam of the Time to Peak Effect (Abolition) and Time to >50% Diminution in Photo-Paroxysmal Response in Patients with Photosensitive Epilepsy" (1)
Time frame: Six weeks
Difference in time (minutes) required between drugs, BRV\& LEV to abolish a PPR (photo-paroxysmal response on the pts encephalogram, EEG) after intermittent photic stimulation (IPS) tested in the same pt of 2 separate occasions. In Pt 1, 8 pts w/photosensitive epilepsy will be studied in double-blind, crossover fashion with 15-minute linear intravenous (i.v.) infusion of either 1500 mg LEV or BRV 100 mg as single dose. After 2 weeks, each pt will be tested in identical fashion w/opposite drug (crossover). Pt 2, Option 1, 8 pts w/photosensitive epilepsy will be studied in double-blind, crossover fashion. Same single mg doses of LEV and BRV will be used, but i.v. infusion time will be 5 minutes;primary outcome measure will be same.Part 2, Option 2, 8 pts w/photosensitive epilepsy will be studied in double-blind, crossover fashion. Single mg i.v. dose of 500 mg LEV or 25 mg BRV will be used, w/infusion time over 15 minutes;primary outcome measure will be the same.
1 secondary outcome
"Comparison between Brivaracetam and Levetiracetam of the Time to Peak Effect (Abolition) and Time to >50% Diminution in Photo-Paroxysmal Response in Patients with Photosensitive Epilepsy" (2)
Time frame: Six weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2019.
- Derived from this study: PubMed 32949370Reed RC, Rosenfeld WE, Lippmann SM, Eijkemans RMJC, Kasteleijn-Nolst Trenite DGA. Rapidity of CNS Effect on Photoparoxysmal Response for Brivaracetam vs. Levetiracetam: A Randomized, Double-blind, Crossover Trial in Photosensitive Epilepsy Patients. CNS Drugs. 2020 Oct;34(10):1075-1086. doi: 10.1007/s40263-020-00761-1.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William E Rosenfeld, M.D. principal investigator
Comprehensive Epilepsy Care Center for Children & Adults
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing BRV vs LEV in randomized double blinded, crossover fashion in people with Photosensitive Epilepsy, run by Rosenfeld, William E., M.D. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
"Comparison between Brivaracetam and Levetiracetam of the Time to Peak Effect (Abolition) and Time to >50% Diminution in Photo-Paroxysmal Response in Patients with Photosensitive Epilepsy" (1) (time frame: Six weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03580707, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2019.